Restoration of blood flow to the ischemic coronary bed initiates the inflammatory process of reperfusion injury, progressive necrosis and apoptosis of myocytes, clinically known as myocardial infarction (MI). Although heparin has broad anti-inflammatory properties, its use as a cardioprotectant is limited by its potent anti-coagulant action. A simple process has now been devised employing reductive alkalinization during lyophilization that selectively and quantitatively removes the 2-O and 3- O sulfates necessary for binding antithrombin III, critical for heparin's anti-coagulant effect. When given at the time of coronary reperfusion, this novel, non-anticoagulant O-desulfated (ODS) heparin prevents neutrophil influx into the ischemic-perfused myocardium, blocks myocyte apoptosis and dramatically reduces infarct size. The ultimate objective is to develop ODS heparin for clinical use to prevent myocyte injury and death in MI. The specific aims of Phase I SBIR will focus on the feasibility of producing GMP quality-drug substance. Pending the successful outcome of these studies, a Phase II SBIR will focus on the scale up of 10 kilos of GMP quality ODS heparin to satisfy the toxicology and PK requirements of an IND submission for its use as a cardioprotectant in MI through Phase II clinical trials. PROPOSED COMMERCIAL APPLICATIONS: Intellectual property: USPTO/EPO with claims to composition, methods of production and use to treat/prevent ischemic reperfusion injury in myocardial infarction (AMI), lung injury & stroke. O-DS heparin is non- anticoagulant, broad-acting anti-inflammatory drug shown to be highly effective in protecting against the irreparable tissue damage caused by reperfusion injury. Use in AMI & stroke alone could exceed $4 billion a year annually worldwide.